Résumé :
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Charcot-Marie-Tooth (CMT) disease is one of the most common inherited neuromuscular disorders, with a prevalence of 17-40 per 100,000 individuals. CMT is classified into two main subgroups, demyelinating (HMSN I or CMT1) and axonal (HMSN II or CMT2), based on electrophysiological criteria. Intermediate forms of CMT have more recently be described and classified. Inheritance can be autosomal dominant (AD), X-linked, or autosomal recessive (AR). The most common form of demyelinating CMT (CMT1A), is caused by a duplication of the PMP22 gene. A deletion of the same gene causes hereditary neuropathy with liability to pressure palsies (HNPP). Point mutations in the PMP22 gene are less common and they may cause either CMT1 or HNPP. We previously described (Kleopa K et al, 2004), four patients from a Cypriot family with a novel PMP22 point mutation (S22F) in which some family members presented with episodes of pressure palsies, while other family members had a slowly progressive chronic polyneuropathy typical of the CMT1 phenotype. We have since identified four additional families and additional patients from the original family with the PMP22 S22F mutation. All families originate from the same village in the Larnaca district of Cyprus thus indicating a founder effect. We hereby present in detail the interesting clinical and electrophysiological characteristics of 17 patients with the PMP22 S22F mutation. Clinically patients present with CMT1, HNPP or a combination of CMT1 and HNPP phenotypes. Eight patients have the CMT1 phenotype, four patients have the HNPP phenotype and five patients have both CMT1 and superimposed HNPP phenotypes. The age of onset varies from 16 to 60 years old and severity is variable among individuals within a family. All the patients were investigated with upper and lower limbs conduction velocities and the median motor nerve conduction velocities ranges from 23 to 33 m/s. Point mutations in PMP22 are rare and may cause either CMT1 or HNPP. We will present, for the first time, a large series of patients carrying the PMP22 S22F point mutation that have been followed up for a long period of time, some of them for over 20 years. The clinical history of the patients the neurological examination as well as the neurophysiological findings will be discussed.
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